| 蔡丹,范英,莫云琪,等.低剂量辐射激活细胞周期蛋白D1的抗辐射作用研究[J].中华放射医学与防护杂志,2025,45(9):840-850.Cai Dan,Fan Ying,Mo Yunqi,et al.Anti-radiation effects of gene CCND1 activated by low-dose radiation[J].Chin J Radiol Med Prot,2025,45(9):840-850 |
| 低剂量辐射激活细胞周期蛋白D1的抗辐射作用研究 |
| Anti-radiation effects of gene CCND1 activated by low-dose radiation |
| 投稿时间：2025-01-20 |
| DOI：10.3760/cma.j.cn112271-20250120-00027 |
| 中文关键词: 低剂量辐射 适应性反应 细胞周期蛋白D1 辐射防护 |
| 英文关键词:Low dose radiation Adaptive response CCND1 Radiation resistance |
| 基金项目:国家自然科学基金面上项目(32271282);国家自然科学基金青年科学基金(82003394) |
| 作者 | 单位 | E-mail | | 蔡丹 | 南华大学衡阳医学院 军事科学院研究生协作培养基地, 衡阳 421001
军事科学院军事医学研究院, 北京 100850 | | | 范英 | 军事科学院军事医学研究院, 北京 100850 | | | 莫云琪 | 南华大学衡阳医学院 军事科学院研究生协作培养基地, 衡阳 421001
军事科学院军事医学研究院, 北京 100850 | | | 刘瑞雪 | 军事科学院军事医学研究院, 北京 100850 | | | 吴磊 | 军事科学院军事医学研究院, 北京 100850 | | | 马佳楠 | 军事科学院军事医学研究院, 北京 100850 | | | 王琪 | 军事科学院军事医学研究院, 北京 100850 | | | 戚振华 | 军事科学院军事医学研究院, 北京 100850 | | | 王治东 | 南华大学衡阳医学院 军事科学院研究生协作培养基地, 衡阳 421001
军事科学院军事医学研究院, 北京 100850 | wangzhidong1977@126.com |
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| 中文摘要: |
| 目的 通过构建低剂量电离辐射诱导适应性反应模型,筛选低剂量辐射激活的内在辐射防护基因,并探究候选基因的辐射抗性作用机制。方法 将细胞分为适应性反应诱导组及全转录组测序组。采用γ-H2AX免疫荧光实验评估DNA损伤水平。通过全转录组测序以及RT-qPCR验证筛选低剂量激活的辐射防护候选基因,并利用CCK-8细胞增殖以及γ-H2AX免疫荧光实验评估候选基因细胞周期蛋白D1(CCND1)的抗辐射作用。上/下调CCND1表达后,经转录组测序分析初步探究其作用机制。结果 构建低剂量电离辐射诱导的淋巴细胞适应性反应模型,筛选出了CCND1、ZMAT3、MGAT3、DFFB、CYP4F2、ITGA6等6个低剂量激活的辐射防护候选基因。与对照组相比,过表达CCND1提高了2 Gy的X射线照射后AHH-1细胞的增殖能力(t = 7.92~14.76,P < 0.05),且DNA损伤水平显著降低(t = 2.79~9.68,P < 0.05)。与对照组相比,敲低CCND1后,细胞增殖能力显著降低(t = 13.58~26.25,P < 0.05),且DNA损伤水平显著增加(t = 2.87~7.61,P < 0.05)。转录组测序发现,上/下调CCND1导致细胞生长与死亡及损伤与修复相关通路被激活。结论 筛选出了6个低剂量激活的辐射防护候选基因,揭示了CCND1在辐射防护中的功能,从低剂量适应性反应的角度为辐射防护剂的开发提供了新的视角。 |
| 英文摘要: |
| Objective To select low-dose radiation-activated genes with intrinsic radiation protection by developing a model for adaptive responses to low-dose ionizing radiation, in order to explore the mechanisms behind the radiation resistance of the candidate genes. Methods The cells were divided into adaptive response induction group and whole transcriptome sequencing group. The level of DNA damage was assessed using the γ-H2AX immunofluorescence assay. The low-dose radiation-activated candidate genes with radiation protection were selected through whole transcriptome sequencing and quantitative reverse transcription PCR (RT-qPCR)-based validation. The anti-radiation effect of candidate gene CCND1 was assessed based on CCK-8 cell proliferation and γ-H2AX immunofluorescence assay. After up- and down-regulation of CCND1 expression, the anti-radiation mechanism of CCND1 was preliminarily explored through transcriptome sequencing analysis. Results A model for low-dose ionizing radiation-induced adaptive responses of lymphocytes was constructed. Using this model, six candidate genes with radiation protection, including CCND1, ZMAT3, MGAT3, DFFB, CYP4F2, ITGA6, were selected. Compared to the control group, overexpressed CCND1 led to significantly enhanced proliferation ability of AHH-1 cells (t = 7.92-14.76, P < 0.05) and distinctly lowered level of DNA damage (t = 2.79-9.68, P < 0.05) after 2 Gy of X-ray irradiation. Furthermore, compared to the control group, the CCND1 knockdown caused significantly decreased cell proliferation ability (t = 13.58-26.25, P < 0.05) and notably elevated level of DNA damage of cells (t = 2.87-7.61, P < 0.05). Transcriptome sequencing revealed that up- and down-regulation of CCND1 expression resulted in the activation of pathways related to cell growth, death, and damage repair. Conclusions By selecting six low-dose-activated candidate genes with radiation protection and revealing the function of CCND1 in radiation protection, this study provides a new perspective for the development of radiation protection agents from the perspective of adaptive responses to low-dose radiation. |
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